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Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease.
Mov Disord. 1997 Nov; 12(6):885-97.MD

Abstract

The molecular characteristics of midbrain dopamine (DA) neurons have been extensively studied in Parkinson's disease (PD). No such studies of the characteristics of midbrain DA neurons in Alzheimer's disease (AD) or Alzheimer's disease with parkinsonism (AD/Park) have been published. We examined the levels of tyrosine hydroxylase (TH) protein, and the expression of TH and dopamine transporter (DAT) mRNAs, in midbrain neurons of PD, AD, and AD/Park cases. In PD, the loss of TH protein in the ventral tier of the substantia nigra pars compacta (SNpc) of the PD group in accompanied by severe losses in the number of neurons that express TH mRNA and DAT mRNA (74% loss). Remaining neurons show a shift to higher concentrations of TH mRNA but a shift to lower concentrations of DAT mRNA per cell. Hence, there is evidence that compensation in the remaining neurons can elevate concentrations of TH mRNA and lower DAT mRNA. Alternatively, there may be a predilection for a loss of neurons with high levels of DAT mRNA and low TH mRNA levels within the SNpc of PD cases. There was no change in TH protein but an elevation of TH mRNA concentrations per neuron without any change in concentrations of DAT mRNA in the AD group. The AD/Park group did not exhibit changes in the level of TH protein, but showed a small loss (26%) of neurons in the SNpc and a greater loss in other regions of the midbrain (43-53%). Remaining DA neurons showed a marked shift to lower concentrations of DAT mRNA per neuron and a nonsignificant shift in cellular concentration of TH mRNA to higher levels. This is consistent with our previous work showing that with AD/Park there is a significant reduction in the number of DAT sites located on DA terminals in the striatum, but the midbrain neurons have not died. Our results indicate that the differential regulation of mRNAs encoding TH and DAT is similar in the parkinsonian disorders (PD and AD/Park) even though the degree of cell death is very different. This might suggest that compensatory events occur in these DA neurons in AD/Park that are similar to those in PD and that result in differential effects on mRNAs encoding TH and DAT proteins.

Authors+Show Affiliations

Thomas H. Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9399211

Citation

Joyce, J N., et al. "Differential Modification of Dopamine Transporter and Tyrosine Hydroxylase mRNAs in Midbrain of Subjects With Parkinson's, Alzheimer's With Parkinsonism, and Alzheimer's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 12, no. 6, 1997, pp. 885-97.
Joyce JN, Smutzer G, Whitty CJ, et al. Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease. Mov Disord. 1997;12(6):885-97.
Joyce, J. N., Smutzer, G., Whitty, C. J., Myers, A., & Bannon, M. J. (1997). Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 12(6), 885-97.
Joyce JN, et al. Differential Modification of Dopamine Transporter and Tyrosine Hydroxylase mRNAs in Midbrain of Subjects With Parkinson's, Alzheimer's With Parkinsonism, and Alzheimer's Disease. Mov Disord. 1997;12(6):885-97. PubMed PMID: 9399211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson's, Alzheimer's with parkinsonism, and Alzheimer's disease. AU - Joyce,J N, AU - Smutzer,G, AU - Whitty,C J, AU - Myers,A, AU - Bannon,M J, PY - 1997/12/17/pubmed PY - 1997/12/17/medline PY - 1997/12/17/entrez SP - 885 EP - 97 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov. Disord. VL - 12 IS - 6 N2 - The molecular characteristics of midbrain dopamine (DA) neurons have been extensively studied in Parkinson's disease (PD). No such studies of the characteristics of midbrain DA neurons in Alzheimer's disease (AD) or Alzheimer's disease with parkinsonism (AD/Park) have been published. We examined the levels of tyrosine hydroxylase (TH) protein, and the expression of TH and dopamine transporter (DAT) mRNAs, in midbrain neurons of PD, AD, and AD/Park cases. In PD, the loss of TH protein in the ventral tier of the substantia nigra pars compacta (SNpc) of the PD group in accompanied by severe losses in the number of neurons that express TH mRNA and DAT mRNA (74% loss). Remaining neurons show a shift to higher concentrations of TH mRNA but a shift to lower concentrations of DAT mRNA per cell. Hence, there is evidence that compensation in the remaining neurons can elevate concentrations of TH mRNA and lower DAT mRNA. Alternatively, there may be a predilection for a loss of neurons with high levels of DAT mRNA and low TH mRNA levels within the SNpc of PD cases. There was no change in TH protein but an elevation of TH mRNA concentrations per neuron without any change in concentrations of DAT mRNA in the AD group. The AD/Park group did not exhibit changes in the level of TH protein, but showed a small loss (26%) of neurons in the SNpc and a greater loss in other regions of the midbrain (43-53%). Remaining DA neurons showed a marked shift to lower concentrations of DAT mRNA per neuron and a nonsignificant shift in cellular concentration of TH mRNA to higher levels. This is consistent with our previous work showing that with AD/Park there is a significant reduction in the number of DAT sites located on DA terminals in the striatum, but the midbrain neurons have not died. Our results indicate that the differential regulation of mRNAs encoding TH and DAT is similar in the parkinsonian disorders (PD and AD/Park) even though the degree of cell death is very different. This might suggest that compensatory events occur in these DA neurons in AD/Park that are similar to those in PD and that result in differential effects on mRNAs encoding TH and DAT proteins. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/9399211/Differential_modification_of_dopamine_transporter_and_tyrosine_hydroxylase_mRNAs_in_midbrain_of_subjects_with_Parkinson's_Alzheimer's_with_parkinsonism_and_Alzheimer's_disease_ L2 - https://doi.org/10.1002/mds.870120609 DB - PRIME DP - Unbound Medicine ER -